The Regulatory Mechanism of the LY6K Gene Expression in Human Breast Cancer Cells

Kong, Hyun Kyung; Yoon, Sukjoon; Park, Jong Hoon

doi:10.1074/jbc.m112.394270

Cited by 26 publications

(31 citation statements)

References 33 publications

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“…In addition, LY6K expression is downregulated by ectopic expression of ERα (Figure 1E and 1F). It was reported that highly upregulated LY6K is related to cell proliferation and metastatic abilities in breast cancer [10]. These findings suggested that ERα could be involved in attenuating metastatic and proliferative capacities and may enhance drug sensitivities in ERα-negative breast cancer.…”

Section: Discussionmentioning

confidence: 95%

“…Recently, LY6K was reported to be a molecular biomarker in breast cancer [7], bladder cancer [8] and esophageal squamous cell carcinomas [9]. In addition, LY6K expression is regulated by the AP-1 transcription factor that promotes cell proliferation, invasive and metastatic abilities in breast cancer cells [10]. Nonetheless, there are few studies to supporting the effect of LY6K on various type of breast cancer.…”

Section: Introductionmentioning

confidence: 99%

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miRNAs involved in LY6K and estrogen receptor α contribute to tamoxifen-susceptibility in breast cancer

et al. 2016

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Estrogen receptor-alpha (ERα) is a clinically important therapeutic target for breast cancer. However, tumors that lose ERα are less responsive to anti-estrogens such as tamoxifen. MicroRNAs (miRNAs) are small RNAs that regulate expression of their target gene and dysregulations of miRNA has been identified in many diseases including human cancer. However, only a few miRNAs associated with tamoxifen resistance has been reported. In this study, we found that lymphocyte antigen 6 complex (LY6K), which is a member of the Ly-6/μPAR superfamily and related to breast cancer progression and metastasis, is inversely correlated with ERα expression. We, for the first time, found miRNAs involved in the regulatory molecular mechanism between ERα and LY6K and related to tamoxifen susceptibility in breast cancer. miR-192-5p, induced by LY6K, downregulates ERα directly and induced tamoxifen resistance in ERα-positive breast cancer cells. In addition, re-expression of ERα in ERα-negative breast cancer cells increased miR-500a-3p expression and directly inhibits LY6K expression. Ectopic expression of miR-500a-3p sensitized ERα-negative cells to tamoxifen by increasing apoptosis. Finally, we observed an inverse correlation between LY6K and ERα in primary breast cancer samples. We found that patients with recurrence showed high expression of miR-192-5p after tamoxifen treatments. In addition, expression of miR-500a-3p was significantly correlated to survival outcome. As miRNAs involved in the regulatory mechanism between LY6K and ERα can affect tamoxifen resistance, downregulating miR-192-5p or re-expressing miR-500a-3p could be a potential therapeutic approach for treating tamoxifen resistant patients.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

miRNAs involved in LY6K and estrogen receptor α contribute to tamoxifen-susceptibility in breast cancer

et al. 2016

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“…Interestingly, all validated targets contained complementarity to the mivaRNAs in their 3 -UTRs (Bellutti et al, 2015). Both microarray and RISC immunoprecipitation approaches also identified the cell-growth protein lymphocyte antigen 6 complex (Aparicio et al, 2010;Bellutti et al, 2015), a protein implicated in both breast, and head and neck cancers (de Nooij-van Dalen et al, 2003;Kong et al, 2012), as a target of 3 -mivaRNAs. Though an increasingly large body of work is focused upon mivaRNA target identification, another layer of complexity is added by the finding that not all AdV small RNAs originate from VA RNAs (Zhao et al, 2013).…”

Section: Dicer Saturationmentioning

confidence: 92%

Adenovirus VA RNA: An essential pro-viral non-coding RNA

Vachon

Conn

2016

Virus Research

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“…Immunoblotting was carried out according to a previously described method using anti-LY6K (I-14; Santa Cruz Biotechnology, Santa Cruz, CA, USA) and anti-β-actin (Bethyl Laboratories, Inc. Montgomery, TX, USA) antibodies [23]. …”

Section: Methodsmentioning

confidence: 99%

Epigenetic activation of LY6K predicts the presence of metastasis and poor prognosis in breast carcinoma

et al. 2016

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The role of lymphocyte antigen 6 complex, locus K (LY6K) in breast cancer has been studied, whereas the epigenetic control of LY6K transcription is not fully understood. Here, we report that breast cancer patients with increased LY6K expression had shorter disease-free and overall survival than the patients with low levels of LY6K by multivariate analysis. LY6K also was upregulated in breast cancer patients with distant metastases than those without distant metastases, downregulating E-cadherin expression. Furthermore, xenograft tumor volumes from LY6K knockdown nude mice were reduced than those of mice treated with control lentivirus. Interestingly, LY6K has a CpG island (CGI) around the transcription start site and non-CGI in its promoter, called a CGI shore. LY6K expression was inversely correlated with methylation in not only CGI but CGI shore, which are associated with histone modifications. Additionally, LY6K methylation was increased by the PAX3 transcription factor due to the SNP242 mutation in LY6K CGI shore. Taken together, breast cancer risk and metastasis were significantly associated with not only LY6K expression, but also methylation of CGI shore which induced by SNP242 mutation. Our results suggest that an understanding epigenetic mechanism of the LY6K gene may be useful to diagnose carcinogenic risk and predict outcomes of patients with metastatic breast cancer.

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The Regulatory Mechanism of the LY6K Gene Expression in Human Breast Cancer Cells

Cited by 26 publications

References 33 publications

miRNAs involved in LY6K and estrogen receptor α contribute to tamoxifen-susceptibility in breast cancer

miRNAs involved in LY6K and estrogen receptor α contribute to tamoxifen-susceptibility in breast cancer

Adenovirus VA RNA: An essential pro-viral non-coding RNA

Epigenetic activation of LY6K predicts the presence of metastasis and poor prognosis in breast carcinoma

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